Trends in mortality, cardiovascular complications, and risk factors in type 2 diabetes.

BACKGROUND: Quality of diabetes care in the Netherlands ranked second in the Euro Diabetes Index 2014, but data on outcomes are lacking. We assessed trends in cardiovascular disease and mortality among type 2 diabetes (T2DM) patients in the context of risk factor control. METHODS: Annual cohorts of adult T2DM patients were constructed from the PHARMO Database Network. Age-standardised mortality rates and incidence rates (IR) of hospitalisations for acute myocardial infarction (AMI), stroke, and congestive heart failure (CHF) were compared with a diabetes-free population matched on age, sex, and general practitioner. Life years lost (LYL) to T2DM or cardiovascular disease were determined by comparing life expectancy between matched groups. Proportions attaining glycated haemoglobin (HbA1c), blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) goals were assessed annually. RESULTS: Among 53,602 T2DM patients, slight increases in IR between 2008 and 2016 were proportional to those in diabetes-free controls; on average T2DM increased the risk of mortality by 86%, hospitalisation for AMI 69%, stroke 57%, and CHF 185%. At age 55, LYL to T2DM averaged 3.5 years and established CVD added 1.8 years, irrespective of sex. HbA1c goal attainment increased from 58% to 65%, LDL-C from 56% to 65%, and systolic BP from 57% to 72%. CONCLUSION: Despite highly organised diabetes care, excess incident cardiovascular events and mortality due to T2DM did not decrease over the study period. Life expectancy of T2DM patients is significantly reduced and risk factor control is suboptimal. This suggests there is considerable room for improvement of diabetes care in the Netherlands.

INR control calculation: comparison of Dutch and international methods.

Results of trials with new oral anticoagulant drugs and vitamin K antagonists (VKA) might not be directly applicable to Dutch clinical practice due to the high level of control of anticoagulation in the Netherlands. In addition, the Dutch method for assessing anticoagulation control uses cross-sectional international normalised ratio (INR) test results while the method used in the trials is based on person-time. To enable comparisons, the two calculation methods were applied to INR data of a cohort of 5422 atrial fibrillation patients treated with VKA. Overall, 74% of test results and 77% of person-time were in the therapeutic range [2.0-3.5]. For the narrower target INR interval [2.5-3.5], 59% of test results and 61% of person-time were in range. It was only between two and six months after the start of treatment that the percentage of person-time in range was lower than the percentage of test results in range. Control of anticoagulation, expressed as a percentage of person-time spent in range, in this Dutch dataset was similar to recent trials with new oral anticoagulants, although it should be noted that the Dutch INR target is higher than the target in these trials. INR control as estimated by the two calculation methods (cross-sectional and longitudinal) was similar.

Risk of major bleeding during concomitant use of antibiotic drugs and coumarin anticoagulants.

BACKGROUND: Coumarin anticoagulants are prone to drug-drug interactions. For example, antibiotic drugs may enhance the anticoagulant effect of coumarins. However, whether such interactions are associated with an increased risk of bleeding, and if so, how frequently this occurs remains unknown. OBJECTIVE: To assess the risk of major bleeding associated with the concomitant use of antibiotic drugs and coumarin anticoagulant therapy. METHODS: We analyzed a retrospective cohort study including all users of acenocoumarol or phenprocoumon in the PHARMO Record Linkage System (age range: 40-80 years). All patients were followed up until end of last coumarin treatment, hospitalization for bleeding, death, or end of study period. For each patient, the number of days on either coumarins alone, or on coumarins in combination with antibiotic drugs was determined. From these data, the relative risks of major bleeding were calculated. RESULTS: A total of 52,102 users of acenocoumarol and 7885 users of phenprocoumon met the inclusion criteria of our study cohort and contributed 139,159 person-years of follow-up. During follow-up, 838 patients (1.4%) were hospitalized for a bleeding while taking coumarins. Of the 62 different antibiotics taken by study members, 19 were associated with a bleeding episode. Of these, 10 were associated with a statistically significant increased bleeding risk. The relative risk of bleeding was three to five for doxycycline, amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, cotrimoxazole, azithromycin and pheneticillin, nine for tetracycline and 43 for cefradine and neomycin. CONCLUSION: Based on relative risks and incidence of use, amoxicillin (alone or with clavulanic acid) and doxycycline are the main antibiotic drugs associated with major bleeding when used in combination with coumarin.

Loss of treatment benefit due to low compliance with bisphosphonate therapy.

UNLABELLED: Among 8,822 new female bisphosphonate users, non-compliant bisphosphonate use was associated with a 45% increased risk of osteoporotic fracture compared to compliant use (MPR >or=80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance. These results emphasize the importance of treatment compliance in obtaining maximal treatment benefit. INTRODUCTION: Bisphosphonates are widely used to treat osteoporosis and reduce fracture risk. Low compliance is frequent and will limit treatment benefit. METHODS: New female users of alendronate or risedronate between 1999-2004, aged >or=45 years were identified from PHARMO-RLS, including drug-dispensing and hospitalization data of >or= 2 million residents of the Netherlands. Patients were followed until first hospitalisation for an osteoporotic fracture, death, or end of study period. Compliance with bisphosphonates during follow-up was measured over 90-day intervals using Medication Possession Ratio (MPR). The association between compliance and fracture risk was analyzed using time-dependent Cox-regression. RESULTS: The study cohort included 8,822 new female bisphosphonate users, contributing in total 22,484 person-years of follow-up. During follow-up, 176 osteoporotic fractures occurred (excluding the first six months). Non-compliant bisphosphonate use was associated with a 45% increased fracture risk compared to compliant use (MPR >or= 80%). Classifying compliance into five categories, fracture risk gradually increased with poorer compliance (p-value <0.05 for trend). A MPR <20% was associated with an 80% increased fracture risk compared to a MPR >or= 90%. CONCLUSIONS: These results show a statistically significant association between level of compliance with bisphosphonates and level of fracture risk, emphasizing the importance of treatment compliance in obtaining maximal treatment benefit.

Utilisation pattern of fentanyl transdermal system in The Netherlands.

PURPOSE: To describe the utilisation pattern of TTS fentanyl in daily practice. METHODS: A retrospective cohort study was performed with data from the Dutch PHARMO system, including medication and hospital admission records of 850,000 inhabitants of 25 Dutch cities. New starters of TTS fentanyl with at least two consecutive prescriptions in the period of 1 January 1996 through 31 December 2001 were included in the study cohort. Patients were distinguished in having non-cancer or cancer pain. RESULTS: About 61% of the patients suffered from non-cancer pain and 60% used other opioids before start of TTS fentanyl. The majority of the patients used other pain medication during the first treatment episode. Most patients (74%) started treatment with the lowest dose of TTS fentanyl (25 microg/hour), patients with cancer pain more often started with higher doses. About half of the patients changed type of patch during the first treatment episode, 80% of these patients had an increase in dose of TTS fentanyl. Fifty percent of all patients had a first treatment episode of less than 2 months and more than one third did not renew their prescription within two months. The median number of days of use per patch was 2.2 days for all patients. CONCLUSIONS: The use of TTS fentanyl is limited to a short period of time for a substantial percentage of patients starting treatment. The median duration of use per TTS fentanyl patch i.e. 2.2 days, was lower than the 3 days application period recommended in the summary of product characteristics.